Neuronal damage is known to occur in specific brain regions after prolonged status epilepticus. Such neuronal damage often has been attributed to hypoxia or ischemia; the cause remains unknown. The present proposal will provide the first comprehensive study of both cerebral oxygen supply and utilization during seizures as well as critically test the hypothesis, already supported by preliminary data, that recurrent seizures are accompanied by cerebral hypoxia. Additional objectives are: 1) to compare cerebral oxygenation during individual seizures vs. recurrent seizures; 2) to examine systemic changes which could contribute to cerebral hypoxia; 3) to examine the possibility that impaired utilization of oxygen contributes to cerebral hypoxia in recurrent seizures; and 4) to test whether administration of higher levels of oxygen can prevent or reverse cerebral hypoxia associated with recurrent seizures. Seizures will be induced periodically with pentylenetetrazol or bicuculline in anesthetized, paralyzed rats. Tissue oxygen levels, relative changes in oxygen utilization by the electron transport chain, and relative changes in blood volume will be monitored simultaneously, and continuously, from the same focal region of cerebral cortex in situ. Local oxygen tension will be recorded polarographically. Changes in blood volume and redox levels of cytochrome oxidase (cytochrome a and a3) will be recorded by dual-beam reflectance spectrophotometry. Arterial blood pressure and blood gas values will be monitored intensively to investigate the influence of systemic changes on the level of cerebral oxygenation during seizures. The proposed studies will provide a critical test of whether oxygen lack occurs in brain during recurrent seizures. Such information is crucial to further understanding of possible mechanisms of neuronal damage. Evaluation of the efficacy, or lack thereof, of increasing inspired oxygen as a means of improving cerebral oxygenation should be of value in treatment of status epilepticus. Understanding the respective roles of systemic and central factors in maintaining adequacy of cerebral oxygenation during seizures may provide a rationale for prevention or amelioration of cerebral hypoxic complications of status epilepticus.